Several reports have suggested that localized alterations in brain metabolism occur after administration of ethanol and other drugs of abuse. General and localized changes in metabolic activity within the brains of rats exposed to various drugs capable of producing physical dependence were studied using the 2-deoxyglucose (2-DG) technique. Specifically, we have studied the chronic (i.e. withdrawal syndrome) and acute effects of ethanol, phenobarbital and diazepam, as well as the effects of diazepam on the ethanol withdrawal syndrome. Similarities and differences were noted in the autoradiographs of animals withdrawing from ethanol, phenobarbital and diazepam. Among the similarities noted were a generalized increase in 2-DG uptake, 400 micrometer wide columns of increased density in the frontal sensorimotor cortex and ovoid areas of increased uptake in the cerebellar vermis. Perhaps the most striking difference noted in the withdrawing animals was the lateral geniculate, in which the dorsal portion showed greater uptake than the ventral portion in the phenobarbital and diazepam withdrawing rats but not in the ethanol withdrawing rats. Detailed quantitative analysis is in progress to determine the similarities and differences in the 2-DG uptake during withdrawal from the various drugs tested. The columns of increased uptake in the frontal sensorimotor cortex and the ovoid areas of increase uptake in the cerebellar vermis seen in the ethanol withdrawal syndrome were no longer apparent after the administration of 5 mg/kg of diazepam. A general decrease in uptake of 2-DG was also noted in those ethanol withdrawing rats given the diazepam when compared to controls. The acute administration of ethanol increased brain glucose metabolism at low doses (0.8 g/kg); at moderate doses (1.6 g/kg) ethanol decreased brain glucose metabolism; and at the high dose (3.2 g/kg) a mixed response to ethanol with respect to glucose metabolism was observed with some nuclei increasing and others decreasing. Acute administration of phenobarbital showed a decrease in 2-DG uptake. No observable effect of acute diazepam was noted. Quantitative analysis of the acute data is in progress.